Continuous positive airway pressure in cluster headache: A randomized, placebo-controlled, triple-blind, crossover study

Background - Oxygen inhalation aborts cluster headache attacks, and case reports show the effect of continuous positive airway pressure. The aim of this study was to investigate the prophylactic effect of continuous positive airway pressure in chronic cluster headache. Methods - This was a randomized placebo-controlled triple-blind crossover study using active and sham continuous positive airway pressure treatment for chronic cluster headache. Patients entered a one month’s baseline period before randomly being assigned to two months’ active continuous positive airway pressure treatment followed by a four weeks’ washout period and two months’ sham continuous positive airway pressure or vice versa. Primary outcome measure was number of cluster headache attacks/week. Results - Of the 30 included participants (12 males, median age 49.5 years, min-max 20–66 years), 25 completed both treatment/sham cycles (two discontinued, three lost to follow-up). The median number of cluster headache attacks per week was reduced from 8.25 (0.75–89.75) attacks to 6.25 (0–56.00) attacks for active continuous positive airway pressure and to 7.50 (0.50–43.75) attacks for sham continuous positive airway pressure, but there was no difference in active versus sham (p = 0.904). One patient had a serious adverse event during active treatment, none occurred during sham treatment. Conclusions - Continuous positive airway pressure treatment did not reduce the number of cluster headache attacks compared to sham treatment in chronic cluster headache patients

Forecasting migraine with machine learning based on mobile phone diary and wearable data

INTRODUCTION: Triggers, premonitory symptoms and physiological changes occur in the preictal migraine phase and may be used in models for forecasting attacks. Machine learning is a promising option for such predictive analytics. The objective of this study was to explore the utility of machine learning to forecast migraine attacks based on preictal headache diary entries and simple physiological measurements. METHODS: In a prospective development and usability study 18 patients with migraine completed 388 headache diary entries and self-administered app-based biofeedback sessions wirelessly measuring heart rate, peripheral skin temperature and muscle tension. Several standard machine learning architectures were constructed to forecast headache the subsequent day. Models were scored with area under the receiver operating characteristics curve. RESULTS: Two-hundred-and-ninety-five days were included in the predictive modelling. The top performing model, based on random forest classification, achieved an area under the receiver operating characteristics curve of 0.62 in a hold-out partition of the dataset. DISCUSSION: In this study we demonstrate the utility of using mobile health apps and wearables combined with machine learning to forecast headache. We argue that high-dimensional modelling may greatly improve forecasting and discuss important considerations for future design of forecasting models using machine learning and mobile health data

Pituitary adenoma and headache

Background: Although headache and pituitary adenoma are two prevalent conditions that may coexist, it has also been postulated that pituitary adenomas may cause secondary headaches that resemble primary headaches. Headache alone is so far a controversial indication for treatment of pituitary adenoma. Purpose: To gain knowledge about the relationship between pituitary tumours and headache, and possible symptomatic effects of treatment. Materials and method: Patients diagnosed with or treated for pituitary adenomas in a 10-year period in a single institution were invited to participate in the study. The 208 (86%) included patients underwent structured telephone interviews concerning current and prior headache complaints while type of tumour, endocrine variables, treatment variables, MRI variables and headache history were recorded from medical records. Headache prevalence among patients was compared to identical measures of headache prevalence from a regional population based study in volunteers. Results: The current cross sectional age and sex-adjusted 1-year prevalence of headache suffering (21%) is significantly lower than the general population (37%) p<0.001. Assessed retrospectively, prevalence of headaches was significantly higher (48%) p<0.001 before being diagnosed with pituitary adenomas than in the general population. With the exception of family history of headache (p=0.020), no associations between headache and measured clinical or radiological variables were identified. Conclusion: Although patients retrospectively reported relief of headache complaints after treatment current prevalence of headaches among patients harbouring both treated and untreated pituitary adenomas is low compared to the general population. Furthermore, the lack of variables associated with headache suggests that headache alone as a sole indication for treatment of pituitary tumours is still debatabl

Sleep-related and non-sleep-related migraine: interictal sleep quality, arousals and pain thresholds

Background: The mechanisms associating sleep and migraine are unknown. No previous polysomnographic (PSG) or pain-threshold (PT) study has compared patients with sleep-related migraine attacks (SM), non-sleep related migraine attacks (NSM) and healthy controls. Methods: We have performed a blinded, prospective exploratory study with case–control design. Thirty-four healthy controls, 15 patients with SM and 18 patients with NSM had interictal PSG heat-, cold- and pressure PT (HPT, CPT, PPT) recordings and completed diary- and questionnaire on sleep and headache related aspects. Results: NSM patients had more slow-wave sleep (SWS) and more K-bursts than SM patients (K-bursts: p = 0.023 and SWS: p = 0.030) and controls (K-bursts: p = 0.009 and SWS: 0.041). NSM patients also had lower HPT and CPT than controls (p = 0.026 and p = 0.021). In addition, SM patients had more awakenings and less D-bursts than controls (p = 0.025 and p = 0.041). Conclusion: SM- and NSM patients differed in objective-, but not subjective sleep quality. NSM patients had PSG findings indicating foregoing sleep deprivation. As foregoing sleep times were normal, a relative sleep deficit might explain reduced PT among NSM patients. The SM patients had signs of slightly disturbed sleep

Habituation of laser-evoked potentials by migraine phase: a blinded longitudinal study

Abstract Background Migraineurs seem to have cyclic variations in cortical excitability in several neurophysiological modalities. Laser-evoked potentials (LEP) are of particular interest in migraine because LEP specifically targets pain pathways, and studies have reported different LEP-changes both between and during headaches. Our primary aim was to explore potential cyclic variations in LEP amplitude and habituation in more detail with a blinded longitudinal study design. Methods We compared N1 and N2P2 amplitudes and habituation between two blocks of laser stimulations to the dorsal hand, obtained from 49 migraineurs with four sessions each. We used migraine diaries to categorize sessions as interictal (> one day from previous and to next attack), preictal (< one day before the attack), ictal or postictal (< one day after the attack). Also, we compared 29 interictal recordings from the first session to 30 controls. Results N1 and N2P2 amplitudes and habituation did not differ between preictal, interictal and postictal phase sessions, except for a post hoc contrast that showed deficient ictal habituation of N1. Habituation is present and similar in migraineurs in the interictal phase and controls. Conclusions Hand-evoked LEP amplitudes and habituation were mainly invariable between migraine phases, but this matter needs further study. Because hand-evoked LEP-habituation was similar in migraineurs and controls, the present findings contradict several previous LEP studies. Pain-evoked cerebral responses are normal and show normal habituation in migraine

Pituitary adenoma and non-acute headache: is there an association, and does treatment help?

Objective Headache is a controversial indication for treatment of pituitary adenoma. We studied the possible relationship between pituitary adenomas and headache as well as the symptomatic effects of treatment. Methods Current and prior headache complaints were assessed in structured telephone interviews in 201 patients with pituitary adenoma. Clinical variables and headache history were retrieved from medical records. Headache prevalence among patients was compared with a regional population-based cohort. Results The presence of headache was higher in patients before the diagnosis of pituitary adenoma compared with the general population (P < 0.001). At follow-up, overall prevalence was lower (P < 0.001), but chronic headache was more prevalent (P = 0.001) than in the general population. With the exception of family history, no associations between headache and clinical or radiologic variables were identified. At follow-up evaluation, 77% of patients with headache reported improvement, 5% reported worsening, and 11% reported new headaches. Patients with nonfunctional adenoma who underwent surgical treatment reported improvement more often (85%) than patients who did not undergo surgery (58%) (P = 0.042). Conclusions In a cohort with both treated and untreated patients with pituitary adenoma, headache prevalence was low compared with the general population. We found no link between clinical or radiologic variables and headache. Although a higher proportion of patients who underwent surgical treatment reported symptomatic relief, most patients who did not undergo treatment also improved. We believe that the unpredictable dynamics of headache over time and the lack of predictive and modifiable tumor-related variables associated with headache or treatment of headache weaken headache as a sole indication for pituitary adenoma treatment.© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0

Biofeedback Treatment App for Pediatric Migraine: Development and Usability Study

Objective The objective of this study was to develop and investigate the usability of a biofeedback treatment smartphone app for adolescent migraine sufferers. Background Biofeedback is effective in treating pediatric migraine. However, biofeedback is not widely used due to the necessity of a trained therapist and specialized equipment. Emerging digital technology, including smartphones and wearables, enables new ways of administering biofeedback. Methods In a prospective open‐label development and usability study, 10 adolescent migraine sufferers used a newly developed biofeedback app with wearable sensors that measured their muscle tension, finger temperature, and heart rate. Three iterative rounds of usability testing, including a 2‐week home testing period, were completed. A biofeedback algorithm, combining and optimizing the 3 physiological modalities, and several algorithms for sham‐treatment were created. Usability was evaluated statistically and summarized thematically. Results Five of ten participants completed all 3 rounds of usability testing. A total of 72 biofeedback sessions were completed. Usability scoring was consistently high, with median scores ranging from 3.5 to 4.5 on a 5‐point scale. The biofeedback optimization algorithm correlated excellently to the raw physiological measurements (r = 0.85, P < .001). The intervention was safe and tolerable. Conclusion We developed an app for young migraine sufferers to receive therapist‐independent biofeedback. The app underwent a rigorous development process as well as usability and feasibility testing. It is now ready for clinical trials

Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study

Background: Our aim was to compare subjective and objective sleep quality and arousal in migraine and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls, interictal, preictal and postictal migraine. Methods: Polysomnography and PT (to pressure, heat and cold) measurements were done in 34 healthy controls and 50 migraineurs. Subjective sleep quality was assessed by sleep diaries, Epworth sleepiness scale, Karolinska sleep questionnaire and Pittsburgh sleep quality index. Migraineurs who had their sleep registration more than 48 h from an attack were classified as interictal while those who were less than 48 h from an attack were classified as either preictal or postictal. Results: Migraineurs reported more insomnia and other sleep-related symptoms than controls, but the objective sleep differences were smaller and we found no differences in daytime sleepiness. Interictal migraineurs had more awakenings (p=0.048), a strong tendency for more slow-wave sleep (p=0.050), lower thermal pain thresholds (TPT) (heat pain thresholds p=0.043 and cold pain thresholds p=0.031) than controls. Migraineurs in the preictal phase had shorter latency to sleep onset than controls (p=0.003). Slow-wave sleep correlated negatively with pressure PT and slow bursts correlated negatively with TPT. Conclusion: Lower PT in interictal migraineurs seems related to increased sleep pressure. We hypothesize that migraineurs on the average suffer from a relative sleep deprivation and need more sleep than healthy controls. Lack of adequate rest might be an attack-precipitating- and hyperalgesia-inducing factor

The relationship between obstructive sleep apnea and insomnia: a population-based cross-sectional polysomnographic study.

Background The relationship between insomnia and objectively measured obstructive sleep apnea (OSA) severity has not previously been investigated in both genders in the general population. The main aim of this population-based polysomnography (PSG) study was to evaluate the cross-sectional association between severity of OSA and DSM-V insomnia and insomnia severity. Methods A random sample of 1200 participants in the third Nord-Trøndelag Health Study (HUNT3) was invited and 213 (18%) aged between 21 and 82 years underwent an ambulatory PSG, a semi-structured interview, and a sleep-specific questionnaire. A proxy DSM-V insomnia diagnosis as well as an Insomnia Symptom Score (ISS, range 0–12) were calculated from three insomnia questions and one daytime sleepiness symptom question. Participants were then divided into three groups according to their apnea-hypopnea index (AHI): AHI < 5 (without OSA), AHI 5–14.9 (mild OSA), and AHI ≥ 15 (moderate-to-severe OSA). Associations between prevalence of insomnia and OSA groups were assessed by logistic regression models adjusted for age and gender. Associations between ISS and OSA were assessed in a general linear model with contrasts. Results A total of 25.2% (29.1% women, 12.5% men) had insomnia. Insomnia prevalence did not differ between subjects with and without OSA, but ISS differed significantly between OSA categories (ANCOVA df 2, F = 6.73, p = 0.001). ISS was lower in the moderate-to-severe OSA-group compared to those without OSA (mean difference −2.68; 95% [CI −4.33, −1.04]; p = 0.002). In subjects with moderate-to-severe OSA, ISS correlated negatively with age (Pearson r = −0.66, p = 0.015). Conclusion In this population-based PSG study, no overall statistical association between OSA and insomnia prevalence was found. However, participants with moderate-to-severe OSA reported less insomnia symptoms than subjects without OSA, in particular in older individuals

Non-invasive cortical modulation of experimental pain in migraine

Objective: To test the hypothesis that secondary somatosensory cortex (S2) is involved in the migraine pathogenesis, by exploring the effect of navigated repetitive transcranial magnetic stimulation (rTMS) to S2 on thermal perception and pain. Methods: In this blinded sham-controlled case-control study of 26 interictal migraineurs and 31 controls, we measured thermal detection and pain thresholds on the hand and forehead, and pain ratings to heat stimulation on the forearm and temple, after real and sham 10 Hz rTMS. Results: rTMS increased cold and heat pain thresholds in controls as compared to interictal migraineurs (p < 0.026). rTMS decreased forehead and arm pain ratings (p < 0.005) and increased hand cool detection thresholds (p < 0.005) in both interictal migraineurs and controls. Conclusions: The effects of rTMS to S2 on thermal pain measures differed significantly between migraine and control subjects, although the effects were generally low in magnitude and not present in pain ratings. However, the lack of cold and heat pain threshold increase in migraineurs may reflect a hypofunction of inhibitory pain modulation mechanisms